Addition Reactions: Regioselectivity

In the previous post on addition, we talked about the key pattern of addition reactions [break C-C π, form two new bonds to adjacent carbons] and how this is the exact opposite pattern of elimination reactions we went through earlier.

Going forward, we’re going to use a lot of structure shortcuts. So it’s helpful to be able to see the “hidden” (or “implicit”) hydrogens that are present when you are looking at alkenes (and alkanes for that matter):

This post is all about one of the important consequences of reactions of alkenes that wasn’t in effect for substitution and acid-base reactions: regioselectivity.

More on that in a sec. Think back to substitution reactions. When a substitution reaction occurs, normally what’s happening is a swapping out of one bond for another on the same carbon. No adjacent atoms are involved [one exception, see Note 1].

With addition reactions, we have the potential to impact two adjacent carbons. If the two new single bonds that are formed are to different atoms, we therefore have the potential to form isomers.

Look at this reaction, for example.

Notice how the two products drawn here? The product on the left is 2-bromopropane, and the product on the right is 1-bromopropane.

How are these compounds related to each other? They’re constitutional isomers [same molecular formula, different connectivity]. In the context of addition reactions, however, there’s another name we can use to describe the relationship between these molecules. Since H and Br add to a different region of the double bond in each case, these can also be called regioisomers.

As it turns out, it’s very rare that two regioisomers are formed in equal yields. In fact, many reactions have a strong preference for forming one regioisomer over the other, a property called “regioselectivity“. The addition of HBr to alkenes is a perfect example. As we’ll see later, the structure of the alkene plays a key role in determining which product is favored.

Note how in the major product, we have formed 1-bromo-1-methyl cyclohexane, and in the minor product, we form 2-bromo-1-methylcyclohexane.

If you don’t understand how this reaction works right now, that’s OK! In a subsequent post, we’ll go through the “how” and “why” details. For now, just focus on the “what” – being able to see the bonds formed and broken, and recognize that these two products are isomers of each other.

Here’s an experimental result from a different reaction called “hydroboration”, where we treat an alkene with borane (BH3) and then sodium hydroxide and hydrogen peroxide. Again, we’ll talk about the mechanism soon, but for now, focus on the bond patterns [again, don’t need to worry about dashes/wedges for now either – all in good time].

Again note how we’re forming regioisomers here. In this reaction, it’s observed that the product on the left is formed in much higher yield than the product on the right.

Here’s another example, in a reaction called “halohydrin formation”. Note the placement of the OH and the Br. See how they’re different? The product on the left is favored.

Not all addition reactions produce regioisomers. For example, “hydrogenation” – treatment of alkenes with a metal catalyst (palladium over carbon or Pd/C) and hydrogen gas – gives the following product. Since we’re forming C-H bonds on both sides of the alkene, it’s not possible to form regioisomers here.

The same is the case for the addition of bromine (Br2) to alkenes. Since we’re forming C-Br on both carbons, regioselectivity isn’t an issue here.

The bottom line I’d want a student to get out of this post is the following:

Go back up through the page and look at the products of each reaction – note how they each follow the key addition pattern (break C-C π, form two new single bonds to carbon)

Be able to identify regioisomers… and be sensitized to this concept, because it’s going to be a key feature of addition reactions!

In the next post, we’re going to go over the same reactions, but focus on the dashes and wedges – in other words, their “stereochemistry”. This will be the second big concept to pay attention to in addition reactions.

About Master Organic Chemistry

After doing a PhD in organic synthesis at McGill and a postdoc at MIT, I applied for faculty positions at universities and it didn’t work out, yada yada yada. So I decided to teach organic chemistry anyway! Master Organic Chemistry is the resource I wish I had when I was learning the subject.